盐酸莫西沙星对映异构体检测

Enantiomeric Separation of Moxifloxacin

and Its(R,R)-Isomer by Ligand-Exchange

Chiral Chromatography

M.Ravikumar1,&,M.Satish Varma1,T.Satyanarayana Raju1,P.Suchitra2,P.Yadagiri Swamy1 1Department of Chemistry,University College of Engineering,Osmania University,Hyderabad500007,India;

E-Mail:ravi20737@

2Matrix Laboratories Limited,ICICI Knowledge Park,Turkapally,Shameerpet Mandal,R.R.Dist.,

Hyderabad,Andhra Pradesh500078,India

Received:21June2008/Revised:20August2008/Accepted:3September2008

Online publication:26October2008

Abstract

A new stereospecific LC method for the separation and quantification of moxifloxacin and its (R,R)-enantiomer in bulk drug was developed and validated by ligand-exchange liquid chromatography on a reversed phase column using aqueous mobile phase containing the chiral reagent L-isoleucine-Cu(II).The UV detector was operated at293nm.Theflow rate of mobile phase was set at0.9mL min-1.The achiral ODS column offers good separation of the two enantiomers in less than20min.The test concentration was1,000l g mL-1in the mobile phase.This method was capable of detecting the(R,R)-enantiomer of moxifloxacin up to0.1l g mL-1for a20l L injection volume.The drug was subjected to stress conditions of hydrolysis,oxidation,photolysis and thermal degradation.There was no interference of degradants with the(R,R)-enantiomer in the developed method.The developed chiral RP-LC method was validated with respect to linearity,accuracy,precision and robustness.The percentage recovery for the(R,R)-enantiomer in bulk drug samples ranged from98.1to 104.4%.The test solution was found to be stable in the mobile phase for48h after prep-aration.

Keywords

Column liquid chromatography

Ligand-exchange liquid chromatography

Forced degradation and validation

Solution and mobile phase stability

Moxifloxacin Introduction

Moxifloxacin hydrochloride belongs to thefluoroquinolone class of anti-infective compounds.The compound has a broad antibacterial spectrum against Gram-positive and Gram-negative organisms including anaerobic bacteria and was developed by scientists at Bayer AG for systemic treatments of respiratory tract infections[1].

Moxifloxacin is produced as a single isomer and an(R,R)-isomer could be present as a chiral impurity(Fig.1). There is no reference in the literature for the enantiomeric separation of moxi-floxacin in the bulk drug substance using liquid chromatography however a nor-mal phase chiral LC method has been described for the separation of two iso-mers of(±)cis-8-benzyl-2,8-diazobicy-clo(4.3.0)nonane,an intermediate of moxifloxacin using a Chiralcel OD-H column[2]and a capillary electrophore-sis method was published for the esti-mation of an enantiomeric purity assay of moxifloxacin hydrochloride[3].

Enantiomers of racemic drugs often differ in pharmacokinetic behaviour or